M Galotto, G Berisso, L Delfino, M Podesta, L Ottaggio, S Dallorso, C Dufour, G B Ferrara, A Abbondandolo, G Dini, A Bacigalupo, R Cancedda, R Quarto
Centro di Biotecnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Experimental hematology 1999 SepBone marrow transplant (BMT) relies on the engraftment of donor hemopoietic precursors in the host marrow space. Colony forming units-fibroblasts (CFU-f), the precursor compartment for the osteogenic lineage, are essential to hemopoietic stem cell survival, proliferation and differentiation. We have studied CFU-f in donors (aged 5 months to 62 years) and in patients who had received allogeneic BMT (aged 2 months to 63 years). In donor marrows we found an inverse correlation between CFU-f frequency and age. In BMT recipients CFU-f frequencies were reduced by 60%-90% (p < 0.05) and the numbers did not recover up to 12 years after transplant. Stromal reconstitution to normal levels was found only in patients < 5 years old. In all patients studied CFU-f post-BMT were of host origin. Patients with low CFU-f levels displayed also a decreased bone mineral density (p < 0.05) and significantly reduced levels of long-term culture-initiating cells (LTC-IC) (p < 0.05). Our study demonstrates that the marrow stromal microenvironment is seriously and irreversibly damaged after BMT. Donor cells do not contribute to reconstitute the marrow microenvironment, whose residual CFU-fs remain of host origin.
M Galotto, G Berisso, L Delfino, M Podesta, L Ottaggio, S Dallorso, C Dufour, G B Ferrara, A Abbondandolo, G Dini, A Bacigalupo, R Cancedda, R Quarto. Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients. Experimental hematology. 1999 Sep;27(9):1460-6
PMID: 10480437
View Full Text